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Computers + Biology = Virus Detector

Joseph DeRisi’s mantelpiece is heavy with awards and prizes. At age 39, Dr. DeRisi, a molecular biologist and biochemist, is a Howard Hughes Medical Investigator; a McArthur “Genius” Fellow; a professor at the University of California, San Francisco; and a winner of this year’s prestigious Heinz Award for Technology, the Economy and Employment. Among his achievements is helping to invent the ViroChip, which greatly accelerates the ability of researchers to diagnose viral infections. An edited version of a two-hour conversation follows.

Q. HOW DID THE IDEA FOR THE VIROCHIP FIRST COME TO YOU?

A. My colleague Dave Wang and I were sitting around the office one day in 2000 asking, “How were viruses discovered in the past?”

We knew that it had always been a laborious and time-consuming effort. When an epidemic struck, what researchers generally did was go to electron microscopes and try to figure out what they were seeing. Sometimes, it took 10, 20 years to find a virus they knew had to be in there.

Earlier, when I was a Stanford graduate student, I’d worked on developing DNA microarrays, which are often called DNA chips. They allow a researcher to do many biological tests at once. The chips are now widely used in gene discovery, cancer detection, drug discovery and toxicology. So Dave and I reasoned that these DNA microarrays would be perfect for viral discovery. I said, “We can build a similar device representing every virus ever discovered, and it could simultaneously look for them.”

A. It’s a glass slide onto which we’ve printed little DNA fragments of every virus ever discovered — about 22,000 different viral sequences. I designed the robot that made the chip. I then built that robot and wrote all the software to automate it. I’ve always been a serious computer nerd, as well as a biologist. Now is really the right moment for a scientist with that combination of interests. The way the chip works is this: If we are looking at a virus and trying to figure out what it is, we take some DNA and some RNA from a patient and we tag it with a fluorescent dye. Then we put that material onto the virus chip. Because matching genetic sequences stick to each other — the double helix — if there’s a match between what’s on the chip and our biological sample, a particular spot on the chip will glow. That tells us which virus the sample is. And, thanks to computers, we can do this with thousands of viruses at one time.

A. It can. The ability to do it relies on evolution. It turns out that viruses evolve from each other, like everything else. So if you look at the evolutionary tree of viruses, you can find parts of their genome that haven’t changed over evolutionary time. You can recognize what may be a new virus by identifying this little piece of their genome that hasn’t changed and is represented on the chip.

Q. IS THAT WHAT YOU DID IN 2003 WITH SARS?

A. Yeah. We had just finished building the full version of our ViroChip, when we read about SARS in the newspapers. We literarily begged the C.D.C. to send us samples of the virus. Once we had it, we immediately put it onto a chip. In less than 24 hours we confirmed that this was a novel coronavirus. We confirmed the ViroChip’s finding by subsequently sequencing this virus’s genome. This had never in history happened before. It was unthinkable five years earlier.

From now on, I don’t think there is going to be any new viral epidemic that we will not be able to identify within a few days. It doesn’t mean you’ll find a cure right away. But you will be able to separate people who have it from those who don’t. You can stop it from spreading, if you have a diagnostic. That’s what got SARS under control.

Q. I UNDERSTAND THAT YOUR CHIP HAS BEEN HELPFUL IN DIAGNOSING SOME AVIAN VIRUSES. IS THAT TRUE?

A. After SARS, we got calls from veterinarians in Israel and Florida who told us that parrots, macaws and cockatiels were dying from this wasting disease, which they suspected was viral. Once we got tissue samples, the ViroChip quickly picked up that this was a bornavirus, something seen in livestock, but that hadn’t been identified in birds before.

As with SARS, once we had a diagnostic tool, you could separate the sick birds from the healthy ones. You might not be able to save an infected bird, but you can certainly stop the epidemic from going any further.

A. Yes, we use DNA microarrays that are similar to the virus chips. Malaria is a one-cell parasite; it’s not a virus. We built a chip that represents that organism’s genome — 6,000 genes. And we grew large amounts of the parasite in vats of human blood. We were then able to use the chip to understand what genetic program these parasites run at the moment they infect human blood cells. This is important because all the clinical symptoms of malaria occur when the parasite infects a person’s blood cells. This knowledge will assist drug and vaccine development.

Before we did this, it was anyone’s guess which of the 6,000 genes were important. Now this data has gone to every malaria lab in the world, and they are picking specific genes to work on, many times based on our data. That’s just amazing!

Q. HAVE YOU PATENTED YOUR VIROCHIP?

A. My colleagues and I considered it. But in the end, we saw no value in doing that. We want people to use this technology. By disseminating the technology freely, more researchers can utilize it faster. And that can produce more rapid advances in human health. We put the specifications into the public domain.

Q. YOU’VE JUST WON THE HEINZ AWARD. WHAT DO YOU PLAN TO DO WITH THE $250,000 PRIZE MONEY?

A. I intend to use a percentage for special research projects on infectious disease, and I’ll give a percentage to field operations working against malaria. After that, I’ll pay my two young daughters’ day care bills and also set up college funds for them.

I did my undergraduate work at the University of California when it was still affordable. But tuition keeps on rising. We’d better start saving now.

A version of this interview appears in print on , on page D2 of the New York edition with the headline: ‘From now on, I don’t think there is going
to be any new viral epidemic that we will
not be able to identify within a few days.’. Order Reprints|Today's Paper|Subscribe